CRYSTAL FORM OF L-GLUFOSINATE AND PREPARATION METHOD AND USE THEREOF

Abstract

The present disclosure is directed to a crystal of L-glufosinate and a preparation method and use thereof. The crystal of L-glufosinate includes five crystal forms, namely crystal form A, crystal form B, crystal form C, crystal form D and crystal form E. These crystal forms show excellent effects in stability, hygroscopicity, storage, etc., which are beneficial to the preparation, separation and storage of herbicides, and at the same time have good solubility and good pharmacokinetics, which is further beneficial to improve the level and speed of herbicides to control weeds.

Claims

1. A crystal of L-glufosinate, wherein, the crystal of L-glufosinate is a crystal form A, a crystal form B, a crystal form C, a crystal form D, or a crystal form E; the crystal form A has an X-ray powder diffraction pattern with characteristic peaks at 2θ of 16.658°±0.2°, 18.139°±0.2°, 23.960°±0.2°, 25.458°±0.2°, and 28.380°±0.2°; the crystal form B has an X-ray powder diffraction pattern with characteristic peaks at 2θ of 9.484°±0.2°, 12.163°±0.2°, 17.098°±0.2°, 22.540°±0.2°, and 34.899°±0.2°; the crystal form C has an X-ray powder diffraction pattern with characteristic peaks at 2θ of 16.018°±0.2°, 19.067°±0.2°, 19.338°±0.2°, and 21.581°±0.2°; the crystal form D has an X-ray powder diffraction pattern with characteristic peaks at 2θ of 8.583°±0.2°, 17.202°±0.2°, 18.398°±0.2°, and 23.001°±0.2°; and the crystal form E has an X-ray powder diffraction pattern with characteristic peaks at 2θ of 8.884°±0.2°, 16.603°±0.2°, 17.459°±0.2°, 18.101°±0.2°, 18.658°±0.2°, and 23.224°±0.2°.

2. The crystal of L-glufosinate according to claim 1, wherein: the X-ray powder diffraction pattern of the crystal form A further has one or both characteristic peaks at 2θ of 9.916°±0.2° and 28.879°±0.2°; the X-ray powder diffraction pattern of the crystal form B further has one or more characteristic peaks at 2θ of 10.833°±0.2°, 19.240°±0.2°, 21.481°±0.2°, 25.202°±0.2°, 32.418°±0.2°, and 34.022°±0.2°; the X-ray powder diffraction pattern of the crystal form C further has one or more characteristic peaks at 2θ of 16.620°±0.2°, 17.460°±0.2°, 29.159°±0.2°, 34.477°±0.2°, and 35.280°±0.2°; the X-ray powder diffraction pattern of the crystal form D further has one or both characteristic peaks at 2θ of 17.738°±0.2°, 21.977°±0.2°, 22.721°±0.2°, and 25.716°±0.2°; and the X-ray powder diffraction pattern of the crystal form E further has one or both characteristic peaks at 2θ of 19.513°±0.2° and 33.221°±0.2°.

3. The crystal of L-glufosinate according to claim 2, wherein: the X-ray powder diffraction pattern of the crystal form A further has one or more characteristic peaks at 2θ of 19.361°±0.2°, 19.859°±0.2°, 21.395°±0.2°, and 21.708°±0.2°; the X-ray powder diffraction pattern of the crystal form B further has one or more characteristic peaks at 2θ of 19.638°±0.2°, 24.879°±0.2°, 27.927°±0.2°, and 37.139°±0.2°; the X-ray powder diffraction pattern of the crystal form C further has one or more characteristic peaks at 2θ of 9.802°±0.2°, 18.139°±0.2°, 19.834°±0.2°, 20.600°±0.2°, 21.984°±0.2°, 23.723°±0.2°, 25.439°±0.2°, 25.738°±0.2°, 26.758°±0.2°, 27.082°±0.2°, 28.395°±0.2°, 30.983°±0.2°, 32.584°±0.2°, 33.100°±0.2°, 34.242°±0.2°, 36.768°±0.2°, 37.075°±0.2°, and 39.535°±0.2°; the X-ray powder diffraction pattern of the crystal form D further has one or more characteristic peaks at 2θ of 32.980°±0.2°, 35.920°±0.2°, and 39.509°±0.2°; and the X-ray powder diffraction pattern of the crystal form E has characteristic peaks at 2θ of 8.884°±0.2°, 16.603°±0.2°, 17.459°±0.2°, 18.101°±0.2°, 18.658°±0.2°, 19.513°±0.2°, 23.224°±0.2°, and 33.221°±0.2°.

4. The crystal of L-glufosinate according to claim 1, wherein: the X-ray powder diffraction pattern of the crystal form A has characteristic peaks at 2θ of 9.916°±0.2°, 16.658°±0.2°, 18.139°±0.2°, 19.361°±0.2°, 19.859°±0.2°, 21.395°±0.2°, 21.708°±0.2°, 23.960°±0.2°, 25.458°±0.2°, 28.380°±0.2°, and 28.879°±0.2°; the X-ray powder diffraction pattern of the crystal form B has characteristic peaks at 2θ of 9.484°±0.2°, 10.833°±0.2°, 12.163°±0.2°, 17.098°±0.2°, 19.240°±0.2°, 19.638°±0.2°, 21.481°±0.2°, 22.540°±0.2°, 24.879°±0.2°, 25.202°±0.2°, 27.927°±0.2°, 32.418°±0.2°, 34.022°±0.2°, 34.899°±0.2°, and 37.139°±0.2°; the X-ray powder diffraction pattern of the crystal form C has characteristic peaks at 2θ of 9.802°±0.2°, 16.018°±0.2°, 16.620°±0.2°, 17.460°±0.2°, 18.139°±0.2°, 19.067°±0.2°, 19.338°±0.2°, 19.834°±0.2°, 20.600°±0.2°, 21.581°±0.2°, 21.984°±0.2°, 23.723°±0.2°, 25.439°±0.2°, 25.738°±0.2°, 26.758°±0.2°, 27.082°±0.2°, 28.395°±0.2°, 29.159°±0.2°, 30.983°±0.2°, 32.584°±0.2°, 33.100°±0.2°, 34.242°±0.2°, 34.477°±0.2°, 35.280°±0.2°, 36.768°±0.2°, 37.075°±0.2°, and 39.535°±0.2°; and the X-ray powder diffraction pattern of the crystal form D has characteristic peaks at 2θ of 8.583°±0.2°, 17.202°±0.2°, 17.738°±0.2°, 18.398°±0.2°, 21.977°±0.2°, 22.721°±0.2°, 23.001°±0.2°, 25.716°±0.2°, 32.980°±0.2°, 35.920°±0.2°, and 39.509°±0.2°.

5. The crystal of L-glufosinate according to claim 1, wherein: the X-ray powder diffraction pattern of the crystal form A is as depicted in FIG. 1; the X-ray powder diffraction pattern of the crystal form B is as depicted in FIG. 3; the X-ray powder diffraction pattern of the crystal form C is as depicted in FIG. 5; the X-ray powder diffraction pattern of the crystal form D is as depicted in FIG. 7; and the X-ray powder diffraction pattern of the crystal form E is as depicted in FIG. 10.

6. The crystal of L-glufosinate according to claim 1, wherein: a spectrum of the crystal form A determined by differential scanning calorimetry shows one endothermic peak, and the peak temperature of the endothermic peak is 129.58±2° C.; a spectrum of the crystal form B determined by differential scanning calorimetry shows one endothermic peak, and the peak temperature of the endothermic peak is 134.07±2° C.; a spectrum of the crystal form C determined by differential scanning calorimetry shows one endothermic peak, and the peak temperature of the endothermic peak is 139.14±2° C.; a spectrum of the crystal form D determined by differential scanning calorimetry shows two endothermic peaks, onset temperatures of the two endothermic peaks are 161.84±2° C. and 199.46±2° C., respectively, and a spectrum of the crystal form D determined by thermogravimetric analysis shows that a weight loss of 4.3±0.2% occurs when heated from 139.5±2° C. to 206.5±2° C.; and a spectrum of the crystal form E determined by differential scanning calorimetry shows three endothermic peaks, onset temperatures of the three endothermic peaks are 95.5±2° C., 147±2° C., and 201±2° C., respectively, and a spectrum of the crystal form E determined by thermogravimetric analysis shows that a weight loss of 1.2±0.2% occurs when heated from 95.5±2° C. to 147±2° C., and a weight loss of 2.89±0.2% occurs when heated from 147±2° C. to 201±2° C.

7. The crystal of L-glufosinate according to claim 1, wherein: a spectrum of the crystal form A determined by differential scanning calorimetry is as depicted in FIG. 2; a spectrum of the crystal form B determined by differential scanning calorimetry is as depicted in FIG. 4; a spectrum of the crystal form C determined by differential scanning calorimetry is as depicted in FIG. 6; a spectrum of the crystal form D determined by differential scanning calorimetry is as depicted in FIG. 8, and a combined spectrum of the crystal form D determined by differential scanning calorimetry and thermogravimetric analysis is as depicted in FIG. 9; and a combined spectrum of the crystal form E determined by differential scanning calorimetry and thermogravimetric analysis is as depicted in FIG. 11.

8. The crystal of L-glufosinate according to claim 1, wherein: the crystal form A is an anhydrous ammonium salt form; the crystal form D is an anhydrous form, and/or, the crystal form D is ammonium salt forms of L-glufosinate; and the crystal form E is an anhydrous form, and/or, the crystal form E is ammonium salt forms of L-glufosinate.

9. A preparation method of a crystal of L-glufosinate according to claim 1, wherein: dispersing L-glufosinate hydrochloride in water to form a dispersion liquid, neutralizing with ammonia gas and controlling the pH of the dispersion liquid to 6-8, concentrating, adding an organic solvent at a temperature T1, and cooling down to −10 to 15° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature, precipitating solid, filtering to obtain the solid, drying the obtained solid, mixing the dried solid with an organic solvent and refluxing, and cooling down to −10 to 15° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature, precipitating solid, filtering to obtain the solid, and drying the obtained solid to give the crystal form A of L-glufosinate, wherein the T1 is between 50° C. and the boiling point of the organic solvent; or dispersing L-glufosinate hydrochloride in water to form a dispersion liquid, neutralizing with ammonia gas and controlling the pH of the dispersion liquid to 6-8, concentrating, controlling the temperature at 20-40° C., adding an organic solvent at a dropping rate of 0.1-10 g/min with precipitation of solid during the dropping process, holding the temperature, and cooling down to −10 to 15° C., holding the temperature, precipitating solid, filtering to obtain the solid, drying the obtained solid, mixing the dried solid with an organic solvent and refluxing, and cooling down to −10 to 15° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature, precipitating solid, filtering to obtain the solid, and drying the obtained solid to give the crystal form A of L-glufosinate; or dispersing L-glufosinate hydrochloride in water to form a dispersion liquid, neutralizing with ammonia gas and controlling the pH of the dispersion liquid to 6-8, concentrating, adding an organic solvent at a temperature T2, and cooling down to −10 to 15° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature, precipitating solid, filtering to obtain the solid, drying the obtained solid to give the crystal form B of L-glufosinate, wherein the T2 is between 50° C. and the boiling point of the organic solvent; or dispersing L-glufosinate hydrochloride in water to form a dispersion liquid, neutralizing with ammonia gas and controlling the pH of the dispersion liquid to 1-4, concentrating, adding an organic solvent at a temperature T3, and cooling down to −10 to 15° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature, precipitating solid, filtering to obtain the solid, drying the obtained solid to give the crystal form C of L-glufosinate, wherein the T3 is between 50° C. and the boiling point of the organic solvent; or adding L-glufosinate ammonium to an organic solvent, heating to 65-90° C. and holding the temperature for the first time, then cooling down to −10 to 35° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature for the second time, precipitating solid, filtering to obtain the solid, and drying the obtained solid to give the crystal form D of L-glufosinate; or adding L-glufosinate ammonium to a mixed solvent of an organic solvent and water, heating to 65-90° C. and holding the temperature for the first time, cooling down to 40 to 60° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature for the second time, then cooling down to −10 to 35° C. at a cooling rate of 1 to 5K between the external temperature and the internal temperature, holding the temperature for the third time, precipitating solid, filtering to obtain the solid, and drying the obtained solid to give the crystal form E of L-glufosinate.

10. The preparation method of the crystal of L-glufosinate according to claim 9, wherein, in the process of preparing the crystal form A, B, C, D or E of L-glufosinate, the organic solvent is selected from a group consisting of an alcohol solvent, a ketone solvent, a nitrile solvent, and combinations thereof.

11. The preparation method of the crystal of L-glufosinate according to claim 10, wherein, the alcohol solvent is selected from a group consisting of methanol, ethanol, isopropanol, and combinations thereof; the ketone solvent includes acetone; the nitrile solvent includes acetonitrile.

12. The preparation method of the crystal of L-glufosinate according to claim 9, wherein, in the process of preparing the crystal form A, crystal form B or crystal form C of L-glufosinate, in the concentration step after introducing ammonia gas, the dispersion liquid is concentrated to 30-80%.

13. The preparation method of the crystal of L-glufosinate according to claim 9, wherein, in the process of preparing the crystal form A, crystal form B or crystal form C of L-glufosinate, the feeding mass ratio of L-glufosinate hydrochloride to the organic solvent is 1:(1-20).

14. The preparation method of the crystal of L-glufosinate according to claim 9, wherein, in the process of preparing the crystal form A, crystal form B or crystal form C of L-glufosinate, the feeding mass ratio of water to the organic solvent is 1:(1-15).

15. The preparation method of the crystal of L-glufosinate according to claim 9, wherein, in one method of preparing the crystal form A of L-glufosinate, the dropping rate of the organic solvent is 1-5 g/min.

16. The preparation method of the crystal of L-glufosinate according to claim 9, wherein, in the process of preparing the crystal form D or E of L-glufosinate, the feeding mass ratio of L-glufosinate ammonium to the organic solvent is 1:(1-20).

17. The preparation method of the crystal of L-glufosinate according to claim 16, wherein, in the process of preparing the crystal form D or E of L-glufosinate, the feeding mass ratio of L-glufosinate ammonium to the organic solvent is 1:(1-10).

18. The preparation method of the crystal of L-glufosinate according to claim 9, wherein, in the process of preparing the crystal form E of L-glufosinate, the feeding mass ratio of water to the organic solvent is (0.05-0.3):1.

19. The preparation method of the crystal of L-glufosinate according to claim 9, wherein: in the process of preparing the crystal form D of L-glufosinate, the holding temperature of the first time of temperature holding is 65-80° C., and the holding time of the first time of temperature holding is 1-15 h; the holding temperature of the second time of temperature holding is 15-35° C., and the holding time of the second time of temperature holding is 1 h-7 days; and in the process of preparing the crystal form E of L-glufosinate, the holding temperature of the first time of temperature holding is 65-80° C., and the holding time of the first time of temperature holding is 1-15 h; the holding temperature of the second time of temperature holding is 45-55° C., and the holding time of the second time of temperature holding is 0.1-3 h; the holding temperature of the third time of temperature holding is 10-30° C., and the holding time of the third time of temperature holding is 1 h-7 days.

20. An herbicide composition, comprising an active ingredient and a carrier, wherein, the active ingredient comprises at least one of the crystal forms A, B, C, D and E of L-glufosinate according to claim 1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0095] FIG. 1 shows the XRPD pattern of the crystal form A of L-glufosinate prepared in Embodiment 1;

[0096] FIG. 2 shows the DSC spectrum of the crystal form A of L-glufosinate prepared in Embodiment 1;

[0097] FIG. 3 shows the XRPD pattern of the crystal form B of L-glufosinate prepared in Embodiment 2;

[0098] FIG. 4 shows the DSC spectrum of the crystal form B of L-glufosinate prepared in Embodiment 2;

[0099] FIG. 5 shows the XRPD pattern of the crystal form C of L-glufosinate prepared in Embodiment 3;

[0100] FIG. 6 shows the DSC spectrum of the crystal form C of L-glufosinate prepared in Embodiment 3;

[0101] FIG. 7 shows the XRPD pattern of the crystal form D of L-glufosinate ammonium prepared in Embodiment 4;

[0102] FIG. 8 shows the DSC spectrum of the crystal form D of L-glufosinate ammonium prepared in Embodiment 4;

[0103] FIG. 9 shows the DSC-TGA combined spectrum of the crystal form D of L-glufosinate ammonium prepared in Embodiment 4;

[0104] FIG. 10 shows the XRPD pattern of the crystal form E of L-glufosinate ammonium prepared in Embodiment 5;

[0105] FIG. 11 shows the DSC-TGA combined spectrum of the crystal form E of L-glufosinate ammonium prepared in Embodiment 5.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0106] In the following, the specific embodiments are combined to further explain the above solutions in detail; it should be understood that, those embodiments are to explain the basic principle, major features and advantages of the present disclosure, and the present disclosure is not limited by the scope of the following embodiments; the implementation conditions employed by the embodiments may be further adjusted according to particular requirements, and undefined implementation conditions usually are conditions in conventional experiments.

[0107] In the following embodiments, unless otherwise specified, all raw materials are basically commercially available or prepared by conventional methods in the field.

[0108] In the present application, the test instruments and conditions used in the experiment are as follows: [0109] 1. The crystal form of the product was analyzed by X-ray powder diffractometer (XRD, Rigaku D/Max-2500 type, Cu Kα radiation, λKα=0.15406 nm), the emission voltage and current were 40 kV and 100 mA, respectively, and the scanning range was 2-40°, the scan step size was 0.02°, and the scan rate was 8°/min. [0110] 2. Differential Scanning calorimetry (DSC) and Thermogravimetric Analysis (TGA): DSC and TGA analyses were performed using a TGA/DSC Model 1 instrument from Mettler Toledo. The DSC measurement method was as follows: take 5-10 mg of the sample into an aluminum crucible, put it into the instrument, set the nitrogen flow rate to 50 ml/min, 200 ml/min, and increase the temperature from 30° C. to 200° C. at a rate of 10° C./min, and analysis was performed using STAR software from Mettler Toledo. The TGA measurement method was as follows: take 5-10 mg of the sample into an aluminum crucible, put it into the instrument, set the nitrogen flow rate to 20 ml/min, 50 ml/min, and increase the temperature from 30° C. to 200° C. at a rate of 10° C./min, and analysis was performed using STAR software from Mettler Toledo.

[0111] In the following, Tj−Tr refers to the “difference between the external temperature and the internal temperature”, wherein the external temperature is equivalent to the temperature of the cooling source (endothermic cooling part), the internal temperature refers to the temperature of the mixed solution, and the cooling rate Tj−Tr=−1 K to −5 K means that the difference between the external temperature and the internal temperature always maintains 1-5° C. during the cooling process, that is, the external temperature and the internal temperature both keep dynamic changes and always maintain a difference of 1-5° C.

Embodiment 1: Preparation of Crystal Form A of L-Glufosinate

[0112] Method 1: L-glufosinate hydrochloride (100 g, 0.46 mol) was added to water (200 g), ammonia gas was introduced to adjust the pH=7, the solution was concentrated under reduced pressure to 75%, methanol (600 g) was added at 60° C., and the solution was cooled down to 5° C. at a cooling rate of Tj−Tr=−2 K, the temperature was held for 24 h, solid was separated out, filtered, and dried, then methanol (300 g) was added to reflux for 24 h, and the solution was cooled down to 5° C. at a cooling rate of Tj−Tr=−2 K, and solid was separated out, filtered, and dried to give the crystal form A of L-glufosinate, with HPLC purity 99%.

[0113] Method 2: L-glufosinate hydrochloride (100 g, 0.46 mol) was added to water (200 g), ammonia gas was introduced to adjust the pH=7, the solution was concentrated under reduced pressure to 50% and cooled down to 30° C., methanol (600 g) was added dropwise at this temperature at a dropping rate of 2 g/min with slow precipitation of solid during the dropping process, after the dropwise addition, the temperature was held for 6 h, then cooled down to 5° C., and the temperature was held for 24 h, the solution was filtered and dried, then methanol (300 g) was added to reflux for 12 h, and the solution was cooled at a cooling rate with a difference of 2K between the external temperature and the internal temperature, and cooled down to 5° C., and kept the temperature to precipitate solid, filtered and dried to the solid to give the crystal form A of L-glufosinate.

[0114] XRPD test was performed on the solid obtained in Method 1, and the pattern was shown in FIG. 1, there were characteristic peaks at diffraction angles 2θ=16.658°, 18.139°, 23.960°, 25.458°, and 28.380°, and the 2θ error range was ±0.2 degrees. Its x-ray powder diffraction data were shown in Table 1.

TABLE-US-00001 TABLE 1 XRPD pattern details of the crystal form A of L-glufosinate Position Relative Relative area [2θ (°)] d spacing [Å] BG intensity [%] [%] FWHM 9.916 8.913 2 41.5 20.8 0.107 16.658 5.317 3 100 100 0.214 18.139 4.8865 3 68.3 45.8 0.143 19.361 4.5807 2 26.8 19.1 0.152 19.859 4.4670 1 23.2 28.2 0.260 21.395 4.1498 2 20.7 31.7 0.327 21.708 4.0906 2 20.7 12.4 0.128 23.960 3.7109 2 53.7 45.2 0.180 25.458 3.4959 2 57.3 48.3 0.180 28.380 3.1422 2 61.0 61.0 0.214 28.879 3.0890 2 31.7 40.4 0.273

[0115] The DSC results (FIG. 2) showed that there was an absorption peak at 129.58° C. (peak temperature); at the same time, based on the standard sample without crystal water, the quantitative content was 99%, and the ammonium content by ion chromatography was 9.0%, which is basically the same as expected from the theoretical monoammonium salt (9.1%), indicating that the crystal form is an anhydrous ammonium salt crystal of glufosinate.

[0116] XRPD test was performed on the solid obtained by Method 2, and the test pattern was substantially the same as depicted in FIG. 1, indicating that the obtained solids are the crystal form A of L-glufosinate.

Embodiment 2: Preparation of Crystal Form B of L-Glufosinate

[0117] L-glufosinate hydrochloride (100 g, 0.46 mol) was added to water (200 g), ammonia gas was introduced to adjust the pH=7, the solution was concentrated under reduced pressure to 50%, methanol (600 g) was added at 60° C., and the solution was cooled down to 5° C. at a cooling rate of Tj−Tr=−2 K, the temperature was held for 5 days, and solid was separated out, filtered, and dried to give the crystal form B of L-glufosinate.

[0118] XRPD test was performed on the obtained solid, and the pattern was shown in FIG. 3, there were characteristic peaks at diffraction angles 2θ=9.484°, 12.163°, 17.098°, 22.540°, and 34.899°, and the 2θ error range is ±0.2 degrees. Its x-ray powder diffraction data were shown in Table 2.

TABLE-US-00002 TABLE 2 XRPD pattern details of the crystal form B of L-glufosinate Position Relative Relative area [2θ (°)] d spacing [Å] BG intensity [%] [%] FWHM 9.484 9.3179 11 100 100 0.077 10.833 8.1600 12 6.8 6.6 0.074 12.163 7.2706 8 42.9 63.0 0.113 17.098 5.1815 7 24.9 27.4 0.085 19.24 4.6093 7 6.0 11.2 0.142 19.638 4.5169 6 2.5 5.3 0.163 21.481 4.1332 6 5.1 8.7 0.130 22.54 3.9415 8 30.4 39.9 0.101 24.879 3.5759 7 3.1 9.3 0.231 25.202 3.5308 7 4.9 6.5 0.103 27.929 3.1919 6 2.6 3.1 0.093 32.418 2.7594 5 6.7 9.0 0.102 34.022 2.6329 6 4.6 7.9 0.132 34.899 2.5688 7 59.2 51.8 0.067 37.139 2.4188 4 1.4 4.3 0.232

[0119] The DSC results (FIG. 4) showed that there was an absorption peak at 134.07° C. (peak temperature); at the same time, based on the standard sample with crystal water, the quantitative content was 92%, and the ammonium content by ion chromatography was 8.4%, which is basically the same as expected from the theoretical monoammonium salt (8.4%), indicating that the crystal form is a crystal of ammonium salt monohydrate.

Embodiment 3: Preparation of Crystal Form C of L-Glufosinate

[0120] L-glufosinate hydrochloride (100 g, 0.46 mol) was added to water (200 g), ammonia gas was introduced to adjust the pH=2.5, the solution was concentrated under reduced pressure to 50%, methanol (300 g) was added at 60° C., and the solution was cooled down to 5° C. at a cooling rate of Tj−Tr=−1K, the temperature was held for 24 h, and solid was separated out, filtered, and dried to give the crystal form C of L-glufosinate.

[0121] XRPD test was performed on the obtained solid, and the pattern was shown in FIG. 5, there were characteristic peaks at diffraction angles 2θ=16.018°, 19.067°, 19.338°, and 21.581°, and the 2θ error range is ±0.2 degrees. Its x-ray powder diffraction data were shown in Table 3.

TABLE-US-00003 TABLE 3 XRPD pattern details of the crystal form C of L-glufosinate Position Relative Relative area [2θ (°)] d spacing [Å] BG intensity [%] [%] FWHM 9.802 9.0161 10 3.1 3.7 0.196 16.018 5.5283 12 30.8 33.1 0.175 16.620 5.3297 15 7.3 6.5 0.147 17.460 5.0749 13 17.5 12.0 0.112 18.139 4.8867 12 4.3 3.2 0.119 19.067 4.6507 14 100 100 0.163 19.338 4.5862 12 45.6 78.9 0.282 19.834 4.4726 16 5.2 3.5 0.109 20.600 4.3081 12 4.5 4.5 0.163 21.581 4.1143 10 33.1 31.7 0.156 21.984 4.0399 12 1.7 1.8 0.177 23.723 3.7474 11 4.9 7.1 0.237 25.439 3.4984 13 3.8 5.1 0.217 25.738 3.4585 14 2.8 2.6 0.152 26.758 3.3289 12 2.3 3.6 0.253 27.082 3.2898 11 2.2 1.7 0.130 28.395 3.1406 12 2.5 4.0 0.263 29.159 3.0600 13 13.2 10.6 0.130 30.983 2.8839 11 5.3 5.8 0.176 32.584 2.7458 13 5.9 5.4 0.147 33.100 2.7041 11 3.8 3.4 0.144 34.242 2.6165 14 6.9 8.7 0.206 34.477 2.5992 15 8.4 9.3 0.180 35.280 2.5419 15 7.7 7.3 0.156 36.768 2.4423 11 2.7 6.7 0.407 37.075 2.4228 13 2.2 5.6 0.422 39.535 2.2775 12 2.8 2.4 0.141

[0122] The DSC results (FIG. 6) showed that there was an absorption peak at 139.14° C. (peak temperature); using the standard sample without crystal water for quantification, the content was 99%, and the ion chromatography analysis showed that the ammonium content was 0.12%, indicating that the crystal form C of L-glufosinate is a zwitterionic crystal form without crystal water.

Embodiment 4: Preparation of Crystal Form D of L-Glufosinate Ammonium

[0123] L-glufosinate ammonium (100 g, 0.48 mol, amorphous) was added to methanol (300 g), the system was heated to 68° C., and the temperature was held for 10 h, the system was cooled down to 25° C. at a cooling rate of Tj−Tr=−1K, the temperature was held for 24 h, and solid was separated out, filtered, and dried to give the crystal form D of L-glufosinate ammonium.

[0124] XRPD test was performed on the obtained crystal form, and the pattern was shown in FIG. 7, there were characteristic peaks at diffraction angles 2θ=8.583°, 17.202°, 18.398°, and 23.001°, and the 2θ error range was ±0.2 degrees, confirming the existence of the new crystal form. Its x-ray powder diffraction data were shown in Table 4.

TABLE-US-00004 TABLE 4 XRPD pattern Position Relative Relative area [2θ (°)] d spacing [Å] BG intensity [%] [%] FWHM 8.583 10.2935 10 29.7 24.8 0.135 17.202 5.1507 10 88.1 70.3 0.129 17.738 4.9960 5 52.5 82.7 0.255 18.398 4.8184 7 100 100 0.162 21.977 4.0411 3 17.8 13.2 0.12 22.721 3.9104 3 13.6 34.4 0.410 23.001 3.8634 2 61.9 86.9 0.227 25.716 3.4613 4 22 13 0.095 32.980 2.7137 3 19.5 20.6 0.171 35.920 2.4981 4 12.7 16.1 0.205 39.509 2.2790 2 12.7 21.0 0.267

[0125] Based on the standard sample without crystal water, the quantitative content was 99.01%, and the ammonium content by ion chromatography was 9.03%, which is basically the same as expected from the theoretical monoammonium salt (9.1%). This crystal is an anhydrous form.

[0126] It was found from the DSC curve that there were two endothermic peaks, the onset temperatures of the two endothermic peaks were 161.84° C. and 199.46° C., respectively, the peak temperatures of the two endothermic peaks were 179.83° C. and 218.80° C., respectively, and absorption of a large amount of heat occurred at 139.5° C., indicating that when compared with other crystal forms, this crystal form is not easy to remove the ammonium group, and has better stability. It could be seen from the TGA spectrum that the weight of the crystal was basically unchanged below 139.5° C., and started to decrease slowly from 139.5° C., which is due to the heat absorption caused by the release of ammonia gas, and decreased rapidly from 206.5° C., which may have undergone phase transition and decomposition.

Embodiment 5: Preparation of Crystal Form E of L-Glufosinate Ammonium

[0127] L-glufosinate ammonium (100 g, 0.48 mol, amorphous) was added to a mixed solution of water (40 g) and methanol (300 g), the system was heated to 68° C., and the temperature was held for 10 h, then the system was cooled down to 50° C. at a cooling rate of Tj−Tr=−1K and the temperature was held for 1 h, then the system was cooled down to 25° C. at a cooling rate of Tj−Tr=−1K and the temperature was held for 24 h, then solid was separated out, filtered, and dried to give the crystal form E of L-glufosinate ammonium.

[0128] XRPD test was performed on the obtained crystal form, and the pattern was shown in FIG. 10, there were characteristic peaks at diffraction angles 2θ=8.884°, 16.603°, 17.459°, 18.101°, 18.658°, and 23.224°, and the 2θ error range was ±0.2 degrees, confirming the existence of the new crystal form. Its x-ray powder diffraction data were shown in Table 5.

TABLE-US-00005 TABLE 5 XRPD pattern Position Relative Relative area [2θ (°)] d spacing [Å] BG intensity [%] [%] FWHM 8.884 9.9453 3 100.0 1219 0.090 16.603 5.3349 2 11.4 222 0.145 17.459 5.0752 3 12.7 191 0.112 18.101 4.8967 3 93.0 1668 0.133 18.658 4.7519 3 17.0 279 0.122 19.513 4.5454 2 6.9 86 0.104 23.224 3.8268 2 14.4 285 0.147 33.221 2.6946 2 7.4 100 0.100

[0129] Based on the standard sample without crystal water, the quantitative content was 97%, and the ammonium content by ion chromatography was 8.81%, which is basically the same as expected from the theoretical monoammonium salt (8.82%). This crystal is an anhydrous form.

[0130] It was found from the DSC curve that there were three endothermic peaks, the onset temperatures of the three endothermic peaks were 95.5±2° C., 147±2° C., and 201±2° C., respectively; the peak temperatures of the three endothermic peaks were 113±2° C., 185.8±2° C., and 226.5±2° C., respectively. Absorption of a small amount of heat occurred at about 95.5° C. and 147° C., and absorption of a large amount of heat occurred at 201° C., indicating that this crystal form is not easy to remove the ammonium group, and has better stability. It could be seen from the TGA spectrum that the weight of the crystal was basically unchanged below 95.5° C., started to decrease slowly by 1.2%, which may be due to the influence of a small amount of impurities, and started to decrease slowly from 147° C., which is due to the heat absorption caused by the release of ammonia gas, and decreased rapidly from 226.5° C., which may have undergone decomposition.

[0131] For the crystal form A, crystal form B, crystal form D and crystal form E of L-glufosinate ammonium, the data comparison of its high temperature stability were shown in Table 6.

TABLE-US-00006 TABLE 6 Comparison of DSC Heat Absorption and Decomposition Temperatures Serial Start of No. Crystal form heat absorption Peak 1 Crystal form A of L-glufosinate 110° C. 129° C. ammonium 2 Crystal form B of L-glufosinate 125° C. 134° C. ammonium 3 Crystal form in CN113831364A 104° C. 115° C. 4 Crystal form D of L-glufosinate 161.84° C. 179.83° C. ammonium 5 Crystal form E of L-glufosinate 147° C. 185.833° C. ammonium

[0132] Experiments show that the new crystal forms A, B, D and E of L-glufosinate ammonium have better high temperature stability than the ammonium salt crystal forms in the existing patent.

Embodiment 6: Preparation of Crystal Form D of L-Glufosinate Ammonium

[0133] L-glufosinate ammonium (100 g, 0.48 mol, the crystal form A of Embodiment 1) was added to methanol (300 g), the system was heated to 68° C., and the temperature was held for 10 h, the system was cooled down to 35° C. at a cooling rate of Tj−Tr=−1K, the temperature was held for 24 h, and solid was separated out, filtered, and dried to give the crystal form D of L-glufosinate ammonium.

[0134] XRPD test was also performed on the obtained solid, and the test pattern was substantially the same as depicted in FIG. 7, indicating that the obtained solid is the crystal form D of L-glufosinate ammonium.

Embodiment 7: Preparation of Crystal Form D of L-Glufosinate Ammonium

[0135] L-glufosinate ammonium (100 g, 0.48 mol, the crystal form B of Embodiment 2) was added to methanol (300 g), the system was heated to 68° C., and the temperature was held for 12 h, the system was cooled down to 25° C. at a cooling rate of Tj−Tr=−1K, the temperature was held for 24 h, and solid was separated out, filtered, and dried to give the crystal form D of L-glufosinate ammonium.

[0136] XRPD test was also performed on the obtained solid, and the test pattern was substantially the same as depicted in FIG. 7, indicating that the obtained solid is the crystal form D of L-glufosinate ammonium.

Embodiment 8: Preparation of Crystal Form E of L-Glufosinate Ammonium

[0137] L-glufosinate ammonium (100 g, 0.48 mol, the crystal form A of Embodiment 1) was added to a mixed solution of water (40 g) and methanol (300 g), the system was heated to 68° C., and the temperature was held for 10 h, then the system was cooled down to 50° C. at a cooling rate of Tj−Tr=−1K and the temperature was held for 1 h, then the system was cooled down to 25° C. at a cooling rate of Tj−Tr=−1K and the temperature was held for 24 h, then solid was separated out, filtered, and dried to give the crystal form E of L-glufosinate ammonium.

[0138] XRPD test was also performed on the obtained solid, and the test pattern was substantially the same as depicted in FIG. 10, indicating that the obtained solid is the crystal form E of L-glufosinate ammonium.

Embodiment 9: Preparation of Crystal Form E of L-Glufosinate Ammonium

[0139] L-glufosinate ammonium (100 g, 0.48 mol, the crystal form B of Embodiment 2) was added to a mixed solution of water (40 g) and methanol (300 g), the system was heated to 68° C., and the temperature was held for 10 h, then the system was cooled down to 50° C. at a cooling rate of Tj−Tr=−1K and the temperature was held for 1 h, then the system was cooled down to 25° C. at a cooling rate of Tj−Tr=−1K and the temperature was held for 24 h, then solid was separated out, filtered, and dried to give the crystal form E of L-glufosinate ammonium.

[0140] XRPD test was also performed on the obtained solid, and the test pattern was substantially the same as depicted in FIG. 10, indicating that the obtained solid is the crystal form E of L-glufosinate ammonium.

Comparative Example

[0141] L-glufosinate hydrochloride (100 g, 0.46 mol) was added to water (200 g), ammonia gas was introduced to adjust the pH=7, the solution was concentrated under reduced pressure to 85%, methanol (600 g) was added at 60° C., and the solution was cooled down rapidly to 20° C. using ice water, and the temperature was held for 7 days, to give a crystal form of L-glufosinate, which was verified to be the crystal form A in the patent CN1110625270A, and after filtration, it had obvious water absorption phenomenon after being placed for 2 days, and it absorbed water and became an aqueous solution.

Embodiment 10: Hygroscopicity Test

[0142] Experimental scheme: 100 g of solids were placed under different humidity for 48 h, and re-measured whether there was a significant change in their quality, and visually inspected whether there was a significant change in their appearance, so as to determine whether the crystal form had hygroscopicity, and the specific results of the crystal forms A, B, and C were shown in Table 7, and the specific results of the crystal forms D and E were shown in Table 8.

TABLE-US-00007 TABLE 7 Weight Serial Crystal Storage change No. form Weight Appearance temperature Humidity (%) 1 A 100.00 g White solid 20° C. 65% +0.02 2 B 100.00 g White solid 20° C. 65% +0.03 3 C 100.00 g White solid 20° C. 65% +0.02 4 A 100.00 g White solid 20° C. 80% +1.45 5 B 100.00 g White solid 20° C. 80% +1.55 6 C 100.00 g White solid 20° C. 80% +1.54

TABLE-US-00008 TABLE 8 Serial Storage Weight Appearance No. Crystal form Weight Appearance temperature Humidity change (%) change 1 Embodiment 100.00 g White 25° C. 65% +0.03 Unchanged 4 powder 2 Embodiment 100.00 g White 25° C. 65% +0.02 Unchanged 5 powder 3 Embodiment 100.00 g White 25° C. 65% +0.03 Unchanged 6 powder 4 Embodiment 100.00 g White 25° C. 65% +0.01 Unchanged 7 powder 5 Embodiment 100.00 g White 25° C. 65% +0.02 Unchanged 8 powder 6 Embodiment 100.00 g White 25° C. 65% +0.02 Unchanged 9 powder 7 Embodiment 100.00 g White 25° C. 80% +1.12 Unchanged 4 powder 8 Embodiment 100.00 g White 25° C. 80% +1.23 Unchanged 5 powder 9 Embodiment 100.00 g White 25° C. 80% +1.17 Unchanged 6 powder 10 Embodiment 100.00 g White 25° C. 80% +1.12 Unchanged 7 powder 11 Embodiment 100.00 g White 25° C. 80% +1.15 Unchanged 8 powder 12 Embodiment 100.00 g White 25° C. 80% +1.18 Unchanged 9 powder

[0143] Experiments show that under the condition of low relative humidity, each crystal form has no obvious hygroscopicity. Under the condition of high relative humidity, each crystal form has very low hygroscopicity.

Embodiment 11: Stability Test

[0144] Experimental method: The crystal forms A, B, and C were stored at a temperature of 60° C. for 7 days, the crystal form changes were re-measured, and the specific results were shown in Table 9.

TABLE-US-00009 TABLE 9 Serial Crystal Temp- No. form Weight erature Humidity Crystal form Appearance 1 A 100 g 60° C. 65% Unchanged Unchanged 2 B 100 g 60° C. 65% Unchanged Unchanged 3 C 100 g 60° C. 65% Unchanged Unchanged

[0145] Experiments show that compared with the crystal forms in CN111065270A, the crystal forms A, B and C of L-glufosinate have excellent stability and are very beneficial to packaging and transportation.

[0146] The crystals obtained in Embodiments 4-9 were stored for 48 days at 25° C. and 60° C., respectively, the crystal form changes were re-measured, and the specific results were shown in Table 10.

TABLE-US-00010 TABLE 10 Serial Weight No. Crystal form Weight Temperature Humidity Crystal form Appearance change (%) 1 Embodiment 4 100 g 25° C. 65% Unchanged Unchanged +0.03 2 Embodiment 5 100 g 25° C. 65% Unchanged Unchanged +0.02 3 Embodiment 6 100 g 25° C. 65% Unchanged Unchanged +0.03 4 Embodiment 7 100 g 25° C. 65% Unchanged Unchanged +0.01 5 Embodiment 8 100 g 25° C. 65% Unchanged Unchanged +0.02 6 Embodiment 9 100 g 25° C. 65% Unchanged Unchanged +0.02 7 Embodiment 4 100 g 60° C. 65% Unchanged Unchanged +0.02 8 Embodiment 5 100 g 60° C. 65% Unchanged Unchanged +0.01 9 Embodiment 6 100 g 60° C. 65% Unchanged Unchanged +0.02 10 Embodiment 7 100 g 60° C. 65% Unchanged Unchanged +0.01 11 Embodiment 8 100 g 60° C. 65% Unchanged Unchanged +0.02 12 Embodiment 9 100 g 60° C. 65% Unchanged Unchanged +0.02

[0147] Experiments show that crystal forms D and E have excellent storage stability at 25° C. and 60° C.

Embodiment 12: Formulation Preparation and Field Efficacy Experiment

[0148] The present disclosure is described in further detail below in conjunction with specific formulation preparation and field efficacy experiments, and the protected crystal forms of this patent meets the requirements of water preparations, and can also be developed into formulations such as single formulation and compound formulation. The following percentages are by weight.

[0149] The combination of preparation processing and field efficacy test was adopted below. The test chemicals were provided by Jiangsu Sevencontinent Green Chemical Co., Ltd., and the formula is shown in Table 11 below.

TABLE-US-00011 TABLE 11 Glufosinate 10% aqueous solution Material name Formula ratio Glufosinate 10% (crystal of L-glufosinate ammonium) Surfactant  3% Water Supplement

[0150] The above-mentioned formulations were prepared with the crystals of the embodiments of the present disclosure and the crystal form A in the patent CN111065270A respectively for field efficacy experiments. It was detected that the physical and chemical properties of the aqueous solution products prepared by each crystal form were stable and met the needs of production and use, and at the same time, field experiments were carried out on different weeds. The dosage was 120 mL/mu.

[0151] Referring to the “Pesticide-Guidelines for the field efficacy trials”, 5 sites were investigated in each plot, each site was 1 square meter, and the types of weeds, the total number of plants, the symptoms of poisoning, the number of dead plants, etc. were recorded for each treatment 7 days after the treatment, and then the results of the plant control effect were counted, and the weed mortality was calculated and counted specifically.

[00001]$\mathrm{Weed}\mathrm{morality}\left(\%\right)=\frac{\mathrm{Number}\mathrm{of}\mathrm{dead}\mathrm{plants}\mathrm{treated}}{\mathrm{Total}\mathrm{number}\mathrm{of}\mathrm{plants}\mathrm{treated}}\times 100\%$

TABLE-US-00012 TABLE 12 Investigation results of plant control effect 7 days after treatment Preparation Plant control effect (%) dosage Alopecurus Euphorbia Treatment Agent (mL/mu) Rumex aequalis helioscopia Bluegrass 1 Crystal form A of 120 100 80 80 80 Embodiment 1 of the present disclosure 2 Crystal form B of 120 100 85 80 80 Embodiment 2 of the present disclosure 3 Crystal form A in 120  95 80 75 75 CN111065270A 4 Crystal form D of Embodiment 4 of 120 100 86 85 85 the present disclosure Crystal form E of 5 Embodiment 5 of 120 100 85 90 85 the present disclosure

Conclusions

[0152] Compared with the crystal form A in the patent CN1110625270, the efficacy of the ammonium salt crystal forms A and B in this patent is obviously 5 to 10% higher. It is speculated that the single ammonium salt crystal form is conducive to the absorption of plants, thereby achieve the effect of weeding.

[0153] Compared with other crystal forms of the ammonium salt, the efficacy of the crystal forms D and E of the ammonium salt in this patent is obviously about 5% higher.

[0154] The embodiments described above are only for illustrating the technical concepts and features of the present disclosure, and are intended to make those skilled in the art being able to understand the present disclosure and thereby implement it, and should not be concluded to limit the protective scope of this disclosure. Any equivalent variations or modifications according to the spirit of the present disclosure should be covered by the protective scope of the present disclosure.

[0155] The endpoints and any values of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For ranges of value, between the end values of each range, between the end values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new ranges of value, and these ranges of value should be considered as specifically disclosed herein.